Gastro-Intestinal Pharmacology GERD PDF

GASTRO-INTESTINAL (GI) PHARMACOLOGY GI PHARMACOLOGY Gastrointestinal Pharmacolgy encompasses of the actions of drugs affecting gastrointestinal system function. These drugs normalize impaired function in the GI tract. The GI tract is the tract or passageway of the digestive system that l...

GASTRO-INTESTINAL (GI) PHARMACOLOGY GI PHARMACOLOGY Gastrointestinal Pharmacolgy encompasses of the actions of drugs affecting gastrointestinal system function. These drugs normalize impaired function in the GI tract. The GI tract is the tract or passageway of the digestive system that leads from the mouth to the anus (oral cavity, pharynx, esophagus, stomach, small intestine, large intestine and anal canal GI PICTURE GASTROESOPHAGEAL REFLUX DISEASE (GERD)  OVERVIEW OF GERD Definition REFLUX : To flow back or return Symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus Gastroesophageal reflux is when whats in the stomach backs up into the esophagus. Classic symptom is frequent and persistent heartburn  NORMAL PHYSIOLOGY FUNCTIONS ESOPHAGUS Transports food from mouth to stomach through peristaltic contractions LOWER ESOPHAGEAL SPHINCTER (LES) Relaxes, on swallowing, to allow food to enter stomach and then contracts to prevent reflux  PATHOGENESIS 3 lines of defense must be impaired for GERD to develop LES barrier impairment Relaxation of LES Low resting LES pressure Increased gastric pressure Decreased clearance of refluxed materials from esophagus Decreased esophageal mucosal resistance  CONTRIBUTING FACTORS Decrease LES pressure  Directly irritate the gastric mucosa Chocolate  Tomato-based products Alcohol  Coffee Fatty meals Coffee, cola, tea  Spicy foods Garlic  Citrus juices Onions  Meds: NSAIDS, aspirin, iron, Smoking Potassium Chloride, alendronate  Stimulate acid secretions  Soda  Beer  Smoking  LINES OF DEFENSE Clearance of refluxed materials from esophagus Primary peristalsis from swallowing – increases salivary flow Secondary peristalsis from esophageal distension Gravitational effects Esophageal mucosal resistance Mucus production in esophagus Bicarbonate movement from blood to mucosa  FACTORS THAT DETERMINE EXTENT OF ESOPHAGEAL DAMAGE: Amount of esophageal damage seen dependent on: Composition of refluxed material Which is worse: acid or alkaline refluxed material?*** Volume of refluxed material Length of contact time of reflux material Natural sensitivity of esophageal mucosa Rate of gastric emptying  TYPICAL SYMPTOMS Common symptoms experienced when pH 3 months GI bleeding and other warning signs Concurrent use of NSAIDS Pregnant or nursing Children < 12 years old  THERAPY GOALS Alleviate or eliminate symptoms Diminish the frequency of recurrence and duration of esophageal reflux Promote healing – if mucosa is injured Prevent complications  THERAPY Therapy is directed at: Increasing LES pressure Enhancing esophageal acid clearance Improving gastric emptying Protecting esophageal mucosa Decreasing acidity of reflux Decreasing gastric volume available to be refluxed  TREATMENT Three phases in treatment Phase I: Lifestyle changes – 2 weeks Lifestyle modifications Patient-directed therapy with OTC medications Phase II: Pharmacologic intervention Standard/high-dose antisecretory therapy Phase III: Surgical intervention Patients who fail pharmacologic treatment or have severe complications of GERD LES positioned within the abdomen where it is under positive pressure  TREATMENT SELECTION Mild intermittent heartburn (Phase I) Treat with lifestyle changes plus antacids Symptomatic relief of mild to moderate GERD (Phase II) Treat with lifestyle changes plus standard doses of proton pump inhibitors (PPI’s) for 4-8 weeks TREATMENT SELECTION Healing of erosive esophagitis or treatment of moderate to severe GERD (Phase II) Lifestyle modifications plus PPI’s for 8-16 weeks PPI’s preferred as initial choice due to more rapid symptom relief and higher rate of healing May also add a PROKINETIC agent in selected patients EXAMPLES OF PROKINETIC AGENTS Metoclopramide Domperidone LIFESTYLE MODIFICATIONS  Elevate the head of the bed 6-8 inches  Decrease fat intake  Smoking cessation  Avoid recumbency for at least 3 hours post-prandial  Weight loss  Limit alcohol intake  Wear loose-fitting clothing  Avoidance of aggravating foods  These changes alone may not control symptoms  Esophageal mucosal resistance: Esophageal Alginic acid ( Gaviscon clearance: LES pressure: Gastric emptying: Metoclopramide Metoclopramide Gastric acid: Antacids PPIs DRUG THERAPY - ANTACIDS Antacids with or without alginic acid Antacids increase LES pressure and do not promote esophageal healing Neutralize gastric acid, causing alkalinization Alginic acid (in Gaviscon) forms a highly viscous solution that floats on top of the gastric contents Dose as needed – typical action – 1-3 hours DRUG THERAPY - ANTACIDS Products: Magnesium salts, aluminum salts, calcium carbonate, and sodium bicarbonate Maalox/Mylanta 30 ml prn or PC & HS Maalox TC/Mylanta II 15 ml prn or PC & HS Gaviscon 2 tabs PC & HS Tums (Calcium Chloride) 0.5-1 gm prn Nugel tabs or suspension DRUG THERAPY - PPI’S Proton Pump Inhibitors Used to treat moderate to severe GERD All agents effective - choose based on cost Omeprazole released OTC 2003 Use for heartburn that occurs ≥ 2 days/week DRUG THERAPY - PPI’S  Standard dosing  Esomeprazole 20 to 40 mg daily  May 2006: FDA approved Nexium for adolescents 12-17 years for the short-term (up to 8 weeks) treatment of GERD  Lansoprazole 15-30 mg daily  Omeprazole 20 to 40 mg daily  Pantoprazole 40 mg daily  Rabeprazole 20 mg daily  Timing  Best is 30 to 60 minutes prior to  DRUG THERAPY - PPI’S May give higher doses bid for Patients with a partial response to standard therapy Patients with breakthrough symptoms Patients with severe esophageal dysmotility Always give second dose 30 to 60 minutes prior to evening meal DRUG THERAPY - PROKINETICS Prokinetic Agents Enhances motility of smooth muscle from esophagus through the proximal small bowel Accelerates gastric emptying and transit of intestinal contents from duodenum DRUG THERAPY - PROKINETICS Prokinetic Agents Results of therapy Improved gastric emptying Enhanced tone of the lower esophageal sphincter Stimulated esophageal peristalsis  PROKINETIC AGENTS - PRODUCTS Metoclopramide Only use if motility dysfunction documented Administer at least 30 minutes prior to meals Dose - 10 to 15 mg before meals and at bedtime SPECIAL POPULATIONS Pregnancy Common, due to decreased LES pressure and increased abdominal pressure Nearly half of all pregnant women experience Antacids generally considered safe, but avoid chronic high doses COUNSELING QUESTIONS Before recommending a therapy, ask: Duration and frequency of symptoms Quality and timing of symptoms Use of alcohol and tobacco Dietary choices Medications already tried to treat symptoms Other disease states present and medications being used CASE STUDY AA, a 45 year old male postal worker, complains of heartburn 3-4 times per month. The pain typically appears after meals. He has tried Tums with varying degrees of success. He would like something “more effective.” CASE STUDY What questions should you ask AA first? What would cause you to refer AA to a physician? What type of GERD do you think AA has- mild, moderate or severe? What treatment should you recommend? QUESTIONS???